No implication of HIV coinfection on the plasma exposure to rifampicin,pyrazinamide, and ethambutol in tuberculosis patients |
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| Authors: | Glauco Henrique Balthazar Nardotto Valdes Roberto Bollela Adriana Rocha Oscar Della Pasqua Vera Lucia Lanchote |
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| Institution: | 1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto Brazil ; 2. Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto Brazil ; 3. Clinical Pharmacology & Therapeutics Group, School of Pharmacy – University College London, London UK |
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| Abstract: | There are contrasting findings regarding the effect of HIV on the pharmacokinetics of first‐line anti‐tubercular drugs (FLATDs) due to a lack of prospective controlled clinical studies, including patients with tuberculosis (TB) and patients with TB living with HIV. This study aims to assess the effect of HIV coinfection and antiviral therapy on the plasma exposure to FLATDs in patients with TB. HIV negative (TB‐HIV− group; n = 15) and HIV positive (TB‐HIV+ group; n = 18) adult patients with TB were enrolled during the second month of FLATDs treatment. All TB‐HIV+ patients were on treatment with lamivudine, tenofovir (or zidovudine), and raltegravir (or efavirenz). Serial blood sampling was collected over 24 h and FLATDs pharmacokinetic parameters were evaluated using noncompartmental methods. In the TB‐HIV+ patients, dose‐normalized plasma exposure area under the curve from zero to 24 h (nAUC0–24; geometric mean and 95% confidence interval CI]) values at steady‐state to rifampicin, pyrazinamide, and ethambutol were 18.38 (95% CI 13.74–24.59), 238.21 (95% CI 191.09–296.95), and 18.33 (95% CI 14.56–23.09) µg∙h/ml, respectively. Similar plasma exposure was found in the TB‐HIV− patients. The geometric mean and 90% CI of the ratios between TB‐HIV− and TB‐HIV+ groups suggest no significant pharmacokinetic interaction between the selected antivirals and FLATDs. Likewise, HIV coinfection itself does not appear to have any effect on the plasma exposure to FLATDs. Study Highlights - WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
First‐line anti‐tubercular drugs (FLATDs) plasma exposure is an important variable of tuberculosis (TB) outcome; however, there are contrasting findings regarding the effect of HIV on the pharmacokinetics of FLATDs due to a lack of prospective controlled clinical studies, including HIV positive and HIV negative patients with TB. - WHAT QUESTION DID THIS STUDY ADDRESS?
This study evaluates the effect of HIV coinfection on the pharmacokinetics of rifampicin, pyrazinamide, and ethambutol in patients who are on stable therapy in the second month of FLATDs treatment. - WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
This study shows no evidence that the pharmacokinetics of rifampicin, pyrazinamide, and ethambutol in patients with TB are affected by HIV coinfection or by any of the standard of care HIV comedications allowed in the study (lamivudine, zidovudine, tenofovir, efavirenz, or raltegravir). - HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
HIV coinfection does not require dose adjustment of rifampicin, pyrazinamide, and ethambutol in patients with TB. |
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